Name of the Postdoctoral Fellow

Name of the Supervisor

Brief Description of Project

Anindita Banerjee

Saumitra Das

COVID-19 pandemic caused by the novel Coronavirus SARS-CoV-2 depicts a strange selectivity with mercurial clinical manifestations among humans. This differential pattern in disease severity, death toll and rate of recovery has been revealed worldwide. Symptoms range from mild cold or development of acute respiratory distress syndrome (ARDS); while few remain asymptomatic. Demographics reveal that potential risk factors include age and underlying co-morbidities; nevertheless, several are often dying without comorbidities due to ARDS. In addition to ecological and viral factors, the host immunogenetic diversity is instrumental in the spectrum of clinical outcomes. Co-ordination of innate and adaptive immune responses can control viral infections, while a compromised immunity augments viral spreading leading to mortality. NK cells, heterogeneous macrophage subsets and T lymphocytes are crucial immune effectors during viral clearance in ARDS. Reports say that elevated pro-inflammatory serum cytokines, chemokines and interferon stimulated genes are associated with disease severity among SARS, MERS and COVID-19 patients. Moreover, critical COVID-19 patients had significant cytokine-upsurge than milder cases. Insufficient evidence exists which could associate COVID-19 disease severity to host immuno-genetic components. This study has been designed to identify, analyze and compare the host-specific immuno-genetic determinants triggering severe lung pathologies among COVID-19 patients, encompassing the endemic settings of India. Molecular characterization of the lung immune microenvironment and functional elucidation of the differentially regulated genes will be done from mild as well as severe COVID-19 patients. The immune determinants trigger disease severity in some, while protecting others might be targeted during drug development. Distinction between these alternative immuno-genetic profiles is essential during vaccine designing against SARS-CoV-2. Genetically predisposed higher-risk groups could be the first to be vaccinated when it becomes available.

Manjarika De

Sreedhar Chinnaswamy

Type III IFN (IFN-λ) family was discovered in 2003 among which IFN-λ4, the newest member was discovered only in 2013. A dinucleotide variant upstream of IFNL3 (IL28B) gives rise to IFN-λ4 by causing a frame-shift in the ORF of the gene. Only a subset of the human population possesses the variant allele ΔG at the dinucleotide polymorphism rs368234815 that causes the frame-shift in exon 1, producing a fully functional IFN-λ4. IFN-λ signaling is apparently restricted to epithelial cells, hepatocytes and some immune cells due to the restricted distribution of the IFN lambda receptor complex (IFNLR). Although, role of type III IFNs in clearance of viruses is widely studied, not much has been explored to ascertain their role in Leishmania infection partly because Leishmaniasis is a neglected tropical disease. Therefore, studying the immunomodulatory role of IFN-λ4 in general and the role of IFN-λs in Leishmaniasis in particular, can lead us to novel paradigms. Moreover, some strong association between PKDL (Post kalazar dermal leishmaniasis) with IFN-λ signaling cannot be undermined as IFNLR are highly expressed in epithelial cells. In this context, my study is aimed at characterizing IFN-λ4’s role as an immunomodulatory cytokine and in characterizing the functions of IFN-λs in Leshmania infections.

Rajiv kumar Mondal

Saumitra Das

Hepatitis C virus (HCV) infection is a worldwide health problem which may lead to acute, chronic hepatitis, liver cirrhosis and hepatocelular carcinoma (HCC). The HCV is a hepatotropic, positive-stranded RNA virus and belongs to the Flaviviridae family. Globally, 177.5 million individuals are infected so far with HCV among which 71 million have chronic HCV infection and in 2016 approximately 399000 people died from HCV related cirrhosis and HCC. In India, so far approximately 12–18 million people are infected with HCV. HCC is the seventh most common cause of cancer-related death in India and more than half of the HCC patients were associated with HCV and Hepatitis B infection. Currently prescribed, Interferon (IFN)-free combinations of direct-acting antivirals (DAAs) can effectively cure HCV infection in more than 95% of individuals except for HCV genotype 3 and it has been observed that HCV genotype 3 is the most prevalent in India followed by genotype 1. In addition, the role of IL28B genetic predictor to the chronic HCV treatment has diminished in the current therapeutic strategy. In this regard, identification of host and viral molecular expression profile during DAA therapy to characterize the influence of genetic factors in the progression of advanced liver disease and functional implication of identified molecular changes in vitro could be helpful for better management of the disease and to identify new therapeutic strategy. This study will help to increase our understanding on the role of host factors in the liver disease progression and will facilitate to identify novel therapeutic targets for the control and prevention of HCV infection and associated advanced liver disease.

Sillarine Kurkalang

Arindam Maitra

Study of intra-tumour heterogeneity associated with tumour recurrence in oral squamous cell carcinoma gingivo-buccal (OSCC-GB)
Oral squamous cell carcinoma gingivo-buccal (OSCC-GB), the most common cancer in India, is mostly diagnosed at advanced stages. Despite advances in treatment modalities, survival rate has not significantly improved over time. Tumour recurrence is common.  Hence, there is an urgent need to understand the underlying mechanism of recurrence. Tumours harbour multiple cell types. The composition of and interactions between these cell types affect growth, metastasis and response to therapy. Current evidence emerging in other cancer types suggest that the intra-tumor heterogeneity plays a role in the ability of solid tumors to evade therapies and thus result in poor prognosis. However, intra-tumour heterogeneity associated with tumour recurrence in OSCC-GB remains to be characterized. Therefore, the present study aims to identify the underlying heterogeneity of cells in tumors of OSCC-GB patients exhibiting tumour recurrence. Single-cell RNA sequencing will be used to identify intra-tumour heterogeneity in OSCC-GB patients (a) who have tumour recurrence within one year of surgery and (b) those who do not have tumour

Sumana Mallick

Sharmila Sengupta

Although cervical cancer incidence is declining in most developed countries, it is still a major threat to Indian women, being the most frequent cause of cancer-related deaths. Persistent infection in the cervical mucosal epithelium with oncogenic Human Papillomavirus (mainly HPV type 16/18) is the major etiology of the disease where oncoproteins E6 and E7 are the key transforming agents that act to drive transformation of the cervical epithelium.  Our lab primarily focuses on the role of HPV16 E7 oncoprotein in cervical cancer pathogenesis and its interaction with various host molecules. The mechanisms by which E7 oncoproteins modulate host transcriptional machinery are still not understood completely. Therefore, my study aims to identify the important genes and pathways that are deregulated due to E7 activity and /or downstream regulation of coding and other non-coding RNAs. To understand how HPV16 E7 oncoprotein targets other cellular transcripts, we would be implementing the high throughput next generation sequencing technologies and relevant in vitro functional assays. This comprehensive approach will be mechanistically insightful and provide a wider grasp of the biology of HPV in such cancers, leading to the identification of more robust target molecules for tackling such cancers.

Trinath Ghosh

Saumitra Das

Role of Modifications in Ribosomal RNA and Proteins in Ribosome Heterogeneity in the Context to Viral infection

Virus often manipulates host cellular processes to replicate its own genome, translation of the viral proteins, along with assembly and release of viral particles. The mechanism of manipulating the host mRNA translation may vary from one virus to other.  Some viruses shut-off the host cap-dependent translation like Enteroviruses. Reports reveal that rotaviruses block transport of polyadenylated mRNA from nucleus to cytoplasm. However, Flavivirus such as dengue virus do not shut-off the host cell protein synthesis; nevertheless they exploit the host ribosome to translate their own RNA. We speculate that there must be some other mechanism such as ribosome heterogeneity. Recent studies indicate that ribosomes are heterogeneous and different ribosome types can preferentially translate specific subsets of mRNAs. Ribosome heterogeneity enables ribosomes to differentially interact with specific set of mRNAs and modulate their expression. Heterogeneity in ribosomal RNA as well as protein composition along with their modification play critical role in normal cellular physiology and diseases including viral diseases as well. In this study, we seek to investigate the modifications in ribosomal proteins and RNA in ribosomal heterogeneity in the context to dengue virus infection.

Vinoth Kumar

Sharmila Sengupta

Persistent infections with human papillomavirus are reported as one of the major risk factors for the development of cervical cancer. In general most HPV infections are cleared by the host immune system while some persist and expresses the viral oncogenes especially E6 and E7 that inactivate the host tumor suppressor proteins p53 and pRB leading to increased genomic instability and accumulation of somatic mutations  and in some case HPV virus integration in the host chromosomes, ultimately resulting in cervical carcinogenesis. Though there has been tremendous improvement in the treatment modalities and the administration of prophylactic vaccines for cervical cancer prevention are in practise in several countries, cervical cancer remains as a serious health problem of women in developing countries. The cervical cancer risk association, histological subtypes and its clinical relevance varies substantially among carcinogenic HPV types but the mechanisms for these differences are poorly understood. My current research is focussed on deciphering host pathogen interaction in cervical cancer by applying next generation based (NGS) whole transcriptome analysis in cervical cancer samples and compared with normal controls followed by pathway analysis and cell linebased experiments to understand the genes / pathways deregulated and its association with cervical cancer development. Besides, I intend to explore the role of non-coding RNAs, specifically miRNAs in cervical cancer pathogenesis and their interactions with the long non-coding RNA, HOTAIR, previously identified as a target of the viral oncoprotein E7, in our laboratory. Taken together, my study is likely to provide insights into the molecular mechanisms driving cervical cancer pathogenesis, leading to the identification of effective therapeutic markers.